P1628: FACTOR XI DEFICIENCY IN CHINESE FEMALE PATIENTS: RESULTS FROM A NATIONWIDE MULTICENTER RETROSPECTIVE STUDY
Authors: Xiyan Wang
Journal: HemaSphere (2023)

Topic: 33. Bleeding disorders (congenital and acquired) Background: Factor XI(FXI) deficiency is a rare and relatively mild bleeding disorder. Despite this, menorrhagia and the increased risk of bleeding during childbirth and surgery remain challenges to female patients with FXI deficiency. To date, data for China is limited. Aims: To describe the clinical manifestations, F11 genotype, management, and outcomes of female patients with FXI deficiency regarding spontaneous bleeding, childbirth, tooth extraction, and surgery. Methods: The study retrospectively analyzed female patients with FXI activity (FXI:C)<50% registered from the National Hemophilia Registration System. The study collected patient characteristics, F11 gene mutations, clinical history, bleeding events, and treatment strategy by telephone follow-up. Results: The study included 118 female patients throughout 23 provincial districts registered in 25 Chinese hemophilia treatment centers. Among these patients, 103 (87.3%) had severe FXI deficiency (FXI:C <15%), and 15 (12.7%) had non-severe FXI deficiency (15%≤FXI:C <50%). The median age was 32 (1–80) years at diagnosis and 37(2–80) years at follow-up. There were 18 patients (15.3%) who reported a family history of bleeding or prolonged activated partial thromboplastin time. Four patients (3.4%) reported having consanguineous marriages in their families. Thirty patients (25.4%) had their F11 gene tested. We detected 26 kinds of variants, including six that have never been reported to the F11 database. The most frequent variants were missense (22, 46.8%) and nonsense mutations (16, 34.0%). Among the genotyped subjects, F11 mutations were homozygous in 9 (30.0%), compound heterozygous in 16 (53.3%), and heterozygous in 5 (16.7%) patients. The mean FXI:C among patients with homozygous/compound heterozygous mutations was significantly lower than among patients with heterozygous mutations (2.5±2.9% vs. 12.0±10.1%, P=0.027). In total, 47 patients (39.8%) reported bleeding symptoms to varying degrees. Thirty-nine patients (33.1%) reported spontaneous bleeding events, including menorrhagia (18.6%), cutaneous bleeding (8.5%), epistaxis (5.1%), oral cavity bleeding (4.2%), prolonged bleeding time after trauma(3.4%), gastrointestinal bleeding(3.4%), haematuria(0.8%), and fatal intracranial hemorrhage(0.8%). Seven(5.9%) of them received replacement therapy treatment. Eighty patients (68.0%) underwent 176 procedures, including 65 vaginal deliveries, 18 cesarean sections, 15 abortions, 27 dental extractions, and 51 other procedures. There were 16 bleeding episodes in total. Forty-two cases received replacement therapy treatment, 37 of which were for prophylactic management, resulting in only three bleeding events occurring during or after surgery. Of the 139 procedures without prophylactic management, the risk of bleeding was higher at sites involving localized hyperfibrinolytic activity than at others(Chi2=6.547, P=0.020). Summary/Conclusion: Most patients with congenital FXI deficiency have no or mild bleeding symptoms. There was good consistency between FXI:C and F11 genotypes. Bleeding often occurs in areas with localized hyperfibrinolytic activity. Our study provided clinical information on Chinese females with FXI deficiency, which may contribute to further exploration and management of this population. Keywords: Real world data, Inherited disease, Coagulation factors, Female